The eukaryotic translation initiation factor eIF4E wears a "cap" for many occasions
The eukaryotic translation initiation factor eIF4E wears a "cap" for many occasions
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DOI：
10.1080/21690731.2016.1220899
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发表时间：
2016-01-01
期刊：
影响因子：
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通讯作者：
Borden, Katherine L. B.
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文献类型：
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作者：
Borden, Katherine L. B.
真核翻译起始因子 eIF4E 在控制蛋白质组的组成中发挥着重要作用。事实上，eIF4E 失调与癌症预后不良有关。传统观点认为 eIF4E 仅在翻译中发挥作用。然而，在过去大约 25 年里，eIF4E 在细胞核中被发现，它在 mRNA 输出中发挥作用；在过去大约 10 年里，eIF4E 在细胞质加工体（P 体）中被发现，它在 mRNA 隔离和稳定性中发挥作用。这些活动的共同生化线索是 eIF4E 结合 mRNA 50 末端的 7-甲基鸟苷帽的能力。最近，eIF4E 独立于帽子直接结合一些 mRNA 元件的可能性也被提出。重要的是，eIF4E 的影响并不是全基因组范围，其目标转录子子集取决于特定 mRNA 元件和上下文相关调节因子的存在。事实上，eIF4E 通过共同调节作用于相同生化途径的转录组的表达来控制 RNA 调节子。此外，过去大约 15 年的研究表明，监管因素采用多种策略以上下文相关的方式调节 eIF4E 活动。这个视角重点关注这些新发现，并将它们纳入更广泛的 eIF4E 功能模型中。
The eukaryotic translation initiation factor eIF4E plays important roles in controlling the composition of the proteome. Indeed, dysregulation of eIF4E is associated with poor prognosis cancers. The traditional view has been that eIF4E acts solely in translation. However, over the last similar to 25 years, eIF4E was found in the nucleus where it acts in mRNA export and in the last similar to 10 years, eIF4E was found in cytoplasmic processing bodies (P-bodies) where it functions in mRNA sequestration and stability. The common biochemical thread for these activities is the ability of eIF4E to bind the 7-methylguanosine cap on the 50 end of mRNAs. Recently, the possibility that eIF4E directly binds some mRNA elements independently of the cap has also been raised. Importantly, the effects of eIF4E are not genome-wide with a subset of transcripts targeted depending on the presence of specific mRNA elements and context-dependent regulatory factors. Indeed, eIF4E governs RNA regulons through co-regulating the expression of groups of transcripts acting in the same biochemical pathways. In addition, studies over the past similar to 15 years indicate that there are multiple strategies that regulatory factors employ to modulate eIF4E activities in context-dependent manners. This perspective focuses on these new findings and incorporates them into a broader model for eIF4E function.